Cisapride is a serotonin 5-HT4 receptor agonist useful as a gastroprokinetic drug. It interacts significantly with several other receptors such as 5-HT2A and 5-HT2C; D2L; 5-HT3A/B; Alpha1A, Alpha2A, Alpha2B and Alpha2C. It was withdrawn from some markets in 2000 due to reports of sudden cardiac arrhythmias. At the origin of this side effect is drug-induced QT prolongation by blockade of the hERG potassium channel (human ether-a-go-go related gene). One of the known pharmacophores of a hERG channel blocker comprises a hydrophilic and a hydrophobic moiety linked by a middle part having a basic nitrogen atom. At physiological pH, the basic nitrogen is protonated and is involved in cation-π interaction with Tyr 652 residues within the hERG channel pore. In order to lower the pKa value of piperidine nitrogen atom, and thereby reduce the likelihood of blockade of the hERG channel, derivatives of cisapride were prepared wherein 3-methoxy-piperidine was replaced by 3-fluoropiperidine and 3,3-difluoropiperidine.